Muscular weakness in the mdx mouse.

mdx mice are believed to be virtually free from neuromuscular symptoms, despite the presence of a degenerative/regenerative process that involves all skeletal muscles. We analyzed both the spontaneous motility and treadmill motor activity of mdx mice aged 15 days to 6 months. Our results indicate that there is an early period, between the end of the second and up to the fifth week of life, when mdx mice experience extreme weakness. After this critical period, both spontaneous motility and endurance of mdx mice, although lower than those of controls, do not show statistically significant differences up to 6 months of age. We also carried out a detailed histological analysis of proximal and distal muscle groups in mdx mice during this early critical motility period. The occurrence of extensive necrosis followed by regeneration and involving proximal muscles before distal ones was documented in mice as young as 16-17 days of age and reached a peak at day 18. We conclude that dystrophin deficiency induces muscle degeneration and significant weakness in mdx mice, but only in an early period. Later on, during development, mdx mice adapt to the lack of this protein and do not show detectable in vivo functional muscle impairment up to 6 months of age.

A comparative study on the effects of the benzodiazepine midazolam and the dopamine agents, apomorphine and sulpiride, on rat behavior in the two-way avoidance test

In recent years. studies in behavioral pharmacology have shown the involvement of dopaminergic mechanisms in avoidance behavior as assessed by the two-way active avoidance test (CAR). Changes in dopaminergic transmission also occur in response to particularly threatening challenges. However, studies on the effects of benzodiazepine (BZD) drugs ill this test are still unclear. Given the interplay of dopamine and other neurotransmitters in the neurobiology of anxiety and schizophrenia the aim of this work was to evaluate the effects of systemic administration of midazolam, the dopaminergic agonist apomorphine, and the D(2) receptor antagonist sulpiride using the CAR, a test that shows good sensitivity to typical neuroleptic drugs. Whereas midazolam did not alter the avoidance response. apomorphine increased and sulpiride reduced them in this test. Escape was not affected by any drug treatments. Heightened avoidance was not associated with the increased motor activity caused by apomorphine. In contrast with the benzodiazepine midazolam, activation of post-synaptic D(2) receptors with apomorphine facilitates, whereas the D(2) receptor antagonism with sulpiride inhibited the acquisition of the avoidance behavior. Together, these results bring additional evidence for a role of D(2) mechanisms in the acquisition of the active avoidance. (C) 2009 Elsevier Inc. All rights reserved.

Efeito da intervenção em esteira motorizada na aquisição da marcha independente e desenvolvimento motor em bebês de risco para atraso desenvolvimental

OBJETIVO: Examinar o efeito de intervenção em esteira motorizada na idade de aquisição da marcha independente em bebês de risco para atraso de desenvolvimento. MÉTODOS: Estudo experimental com 15 lactentes a partir do 5º mês de idade, sendo cinco deles com risco de atraso de desenvolvimento submetidos a sessões de fisioterapia e intervenção em esteira motorizada (Grupo Experimental); cinco com risco de atraso de desenvolvimento submetidos apenas a sessões de fisioterapia (Grupo Controle de Risco); e cinco bebês sem risco de atraso (Grupo Controle Típico). As sessões de fisioterapia ocorreram duas vezes por semana, seguidas de intervenção em esteira motorizada para o grupo experimental. Todos os bebês foram avaliados mensalmente pela Alberta Infant Motor Scale e os participantes do grupo experimental foram filmados durante a realização das passadas na esteira. Comparações entre os grupos ao longo do tempo foram realizadas por análise de variância (ANOVA) e de multivariância (MANOVA). RESULTADOS: Os bebês do Grupo Experimental adquiriram a marcha independente aos 12,8 meses e os do Grupo Controle de Risco aos 13,8 meses de idade corrigida, sendo que a aquisição do Grupo Controle de Risco ocorreu mais tarde em relação ao Grupo Controle Típico (1,1 meses; p<0,05). Os bebês do grupo experimental apresentaram padrão alternado das passadas na esteira, que aumentou ao longo da intervenção (p<0,05), e mostraram melhora do desenvolvimento motor global em relação aos bebês do Grupo Controle de Risco. CONCLUSÕES: A esteira pode ser considerada um agente facilitador para a aquisição do andar independente e do desenvolvimento motor global de bebês com risco de atraso de desenvolvimento.

Síntomas depresivos y trastorno motor en pacientes con enfermedad de Parkinson

Introduction. Complex relations between brain and psychopathology have attracted the interest of researchers, aiming to clarify the neurobiological mechanisms of depression in Parkinson's disease, obviously in addiction to mental features. Aims. The association of motor impairment and decline of personal autonomy with severity of depressive symptoms was the hypothesis of the present study. Aiming to check this hypothesis, the objective of this study consisted in investigating relationships between the severity of depressive symptoms and motor characteristics of Parkinson's disease. Patients and methods. Thirty patients (53 to 80 year-old) with medical diagnosis of idiopathic Parkinson's disease in initial clinic stages were studied. The Unified Parkinson's Disease Rating Scale, Hoehn-Yahr Scale, and Schwab & England Scale were used to assess the clinic signs and symptoms. The depressive symptoms were identified by complete anamnesis, examination of mental condition, and the Hamilton Rating Scale for Depression and the Anxiety and Depression Scale. Statistical analysis was performed by Pearson's correlation and multiple regression analysis. Results. A significant correlation of severity of depression symptoms with disease stage (p < 0.02), with motor signs (p < 0.008), and with functional performance (p < 0.007) was found. Conclusion. There was significant association between motor impairment and severity of depressive symptoms, and between depression and early disease onset or prolonged duration of Parkinson's disease. © 2007, Revista de Neurología.

Motor intervention in children with school learning difficulties

This study sought to evaluate motor development in children aged 6 to 11 years with learning difficulties and school characteristics of delayed motor development, before and after application of a motor intervention program. The sample consisted of 28 children with a mean age of 107.21 ± 16.56 months, who were evaluated by the Motor Development Scale and received motor intervention for 6 months, followed by reassessment. We observed a statistically significant difference between the average of the motor activity ratios in all areas of the evaluation and reevaluation. Also verified in the evaluation were the concentration ratios of children with motor activity greater than or equal to 80 and there was a revaluation increase in this concentration on re-evaluation, the areas with the greatest increase in concentration and significant differences being: Body Schema, Space and temporal Organization. In the overall evaluation of MDS, most children presented the classification of low normal. However, in the reassessment most have evolved into the average normal, only 4 of themremaining in the same classification. Therefore, in this study, children with learning disabilities also showed motor deficits and the intervention applied contributed to an increase in the motor ratios with consequent improvement in motor development. Besides psychopedagogical asistance, it is essential to reassess them and if necessary apply the intervention in the motor development of children with learning difficulties.

Motor readiness and joint torque production in lower limbs of older women fallers and non-fallers

This study aimed to evaluate the motor response time and ability to develop joint torque at the knee and ankle in older women with and without a history of falls, in addition to investigating the effect of aging on these capacities. We assessed 18 young females, 21 older female fallers and 22 older female non-fallers. The peak torque, rate of torque development, rate of electromyography (EMG) rise, reaction time, premotor time and motor time were obtained through a dynamometric assessment and simultaneous electromyography. Surface EMGs of the rectus femoris (RF), vastus lateralis (VL), biceps femoris (BF), gastrocnemius lateralis (GL) and tibialis anterior (TA) muscles were recorded. Knee extension and flexion peak torques were lower in older fallers than in non-fallers. Knee extension and flexion and ankle plantarflexion and dorsiflexion peak torques were lower in both older groups than in the younger group. The rate of EMG rise of the BF and the motor time of the TA were lower and higher, respectively, in older fallers than in the younger adults. The time to reach peak torque in knee extension/flexion and ankle plantarflexion/dorsiflexion and the motor times of the RF, VL, BF and GL were higher in both older groups than in the younger groups. The motor time of the TA during ankle dorsiflexion and the knee extension peak torque were the major predictors of falls in older women, accounting for approximately 28% of the number of falls. Thus, these results further reveal the biomechanical parameters that affect the risk of falls and provide initial findings to support the prescription of exercises in fall prevention programs. © 2013 Elsevier Ltd.

Single early prenatal lipopolysaccharide exposure impairs striatal monoamines and maternal care in female rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Early and current physical activity: relationship with intima-media thickness and metabolic variables in adulthood

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Cortico-cortical white matter motor pathway microstructure is related to psychomotor retardation in major depressive disorder

Alterations of brain structure and function have been associated with psychomotor retardation in major depressive disorder (MDD). However, the association of motor behaviour and white matter integrity of motor pathways in MDD is unclear. The aim of the present study was to first investigate structural connectivity of white matter motor pathways in MDD. Second, we explore the relation of objectively measured motor activity and white matter integrity of motor pathways in MDD. Therefore, 21 patients with MDD and 21 healthy controls matched for age, gender, education and body mass index underwent diffusion tensor imaging and 24 hour actigraphy (measure of the activity level) the same day. Applying a probabilistic fibre tracking approach we extracted connection pathways between the dorsolateral prefrontal cortex (dlPFC), the rostral anterior cingulate cortex (rACC), the pre-supplementary motor area (pre-SMA), the SMA-proper, the primary motor cortex (M1), the caudate nucleus, the putamen, the pallidum and the thalamus. Patients had lower activity levels and demonstrated increased mean diffusivity (MD) in pathways linking left pre-SMA and SMA-proper, and right SMA-proper and M1. Exploratory analyses point to a positive association of activity level and mean-fractional anisotropy in the right rACC-pre-SMA connection in MDD. Only MDD patients with low activity levels had a negative linear association of activity level and mean-MD in the left dlPFC-pre-SMA connection. Our results point to structural alterations of cortico-cortical white matter motor pathways in MDD. Altered white matter organisation of rACC-pre-SMA and dlPFC-pre-SMA pathways may contribute to movement initiation in MDD.

Maternal and Postweaning High-Fat Diets Disturb Hippocampal Gene Expression, Learning, and Memory Function

We tested the hypothesis that excess saturated fat consumption during pregnancy, lactation, and/or postweaning alters the expression of genes mediating hippocampal synaptic efficacy and impairs spatial learning and memory in adulthood. Dams were fed control chow or a diet high in saturated fat before mating, during pregnancy, and into lactation. Offspring were weaned to either standard chow or a diet high in saturated fat. The Morris Water Maze was used to evaluate spatial learning and memory. Open field testing was used to evaluate motor activity. Hippocampal gene expression in adult males was measured using RT-PCR and ELISA. Offspring from high fat-fed dams took longer, swam farther, and faster to try and find the hidden platform during the 5-day learning period. Control offspring consuming standard chow spent the most time in memory quadrant during the probe test. Offspring from high fat-fed dams consuming excess saturated fat spent the least. The levels of mRNA and protein for brain-derived neurotrophic factor and activity-regulated cytoskeletal-associated protein were significantly decreased by maternal diet effects. Nerve growth factor mRNA and protein levels were significantly reduced in response to both maternal and postweaning high-fat diets. Expression levels for the N-methyl-D-aspartate receptor (NMDA) receptor subunit NR2B as well as synaptophysin were significantly decreased in response to both maternal and postweaning diets. Synaptotagmin was significantly increased in offspring from high fat-fed dams. These data support the hypothesis that exposure to excess saturated fat during hippocampal development is associated with complex patterns of gene expression and deficits in learning and memory.

The lifestyle of our kids (LOOK) project: outline of methods

This methods paper outlines the overall design of a community-based multidisciplinary longitudinal study with the intent to stimulate interest and communication from scientists and practitioners studying the role of physical activity in preventive medicine. In adults, lack of regular exercise is a major risk factor in the development of chronic degenerative diseases and is a major contributor to obesity, and now we have evidence that many of our children are not sufficiently active to prevent early symptoms of chronic disease. The lifestyle of our kids (LOOK) study investigates how early physical activity contributes to health and development, utilizing a longitudinal design and a cohort of eight hundred and thirty 7-8-year-old (grade 2) school children followed to age 11-12 years (grade 6), their average family income being very close to that of Australia. We will test two hypotheses, that (a) the quantity and quality of physical activity undertaken by primary school children will influence their psychological and physical health and development; (b) compared with existing practices in primary schools, a physical education program administered by visiting specialists will enhance health and development, and lead to a more positive perception of physical activity. To test the first hypothesis we will monitor all children longitudinally over the 4 years. To test the second we will involve an intervention group of 430 children who receive two 50min physical education classes every week from visiting specialists and a control group of 400 who continue with their usual primary school physical education with their class-room teachers. At the end of grades 2, 4, and 6 we will measure several areas of health and development including blood risk factors for chronic disease, cardiovascular structure and function, physical fitness, psychological characteristics and perceptions of physical activity, bone structure and strength, motor control, body composition, nutritional intake, influence of teachers and family, and academic performance.

A model of ocular dominance column development by competition for trophic factor

Recent experimental evidence has shown that application of certain neurotrophic factors (NTs) to the developing primary visual cortex prevents the development of ocular dominance (OD) columns. One interpretation of this result is that afferents from the lateral geniculate nucleus compete for postsynaptic trophic factor in an activity-dependent manner. Application of excess trophic factor eliminates this competition, thereby preventing OD column formation. We present a model of OD column development, incorporating Hebbian synaptic modification and activity-driven competition for NT, which accounts for both normal OD column development as well as the prevention of that development when competition is removed. In the “control” situation, when available NT is below a critical amount, OD columns form normally. These columns form without weight normalization procedures and in the presence of positive inter-eye correlations. In the “experimental” case, OD column development is prevented in a local neighborhood in which excess NT has been added. Our model proposes a biologically plausible mechanism for competition between neural populations that is motivated by several pieces of experimental data, thereby accounting for both normal and experimentally perturbed conditions.

Inhibition of calcium/calmodulin kinase II alpha subunit expression results in epileptiform activity in cultured hippocampal neurons

Several models that develop epileptiform discharges and epilepsy have been associated with a decrease in the activity of calmodulin-dependent kinase II. However, none of these studies has demonstrated a causal relationship between a decrease in calcium/calmodulin kinase II activity and the development of seizure activity. The present study was conducted to determine the effect of directly reducing calcium/calmodulin-dependent kinase activity on the development of epileptiform discharges in hippocampal neurons in culture. Complimentary oligonucleotides specific for the α subunit of the calcium/calmodulin kinase were used to decrease the expression of the enzyme. Reduction in kinase expression was confirmed by Western analysis, immunocytochemistry, and exogenous substrate phosphorylation. Increased neuronal excitability and frank epileptiform discharges were observed after a significant reduction in calmodulin kinase II expression. The epileptiform activity was a synchronous event and was not caused by random neuronal firing. Furthermore, the magnitude of decreased kinase expression correlated with the increased neuronal excitability. The data suggest that decreased calmodulin kinase II activity may play a role in epileptogenesis and the long-term plasticity changes associated with the development of pathological seizure activity and epilepsy.

Long-term change in the organization of inventive activity

Relying on a quantitative analysis of the patenting and assignment behavior of inventors, we highlight the evolution of institutions that encouraged trade in technology and a growing division of labor between those who invented new technologies and those who exploited them commercially over the nineteenth and early-twentieth centuries. At the heart of this change in the organization of inventive activity was a set of familiar developments which had significant consequences for the supply and demand of inventions. On the supply side, the growing complexity and capital intensity of technology raised the amount of human and physical capital required for effective invention, making it increasingly desirable for individuals involved in this activity to specialize. On the demand side, the growing competitiveness of product markets induced firms to purchase or otherwise obtain the rights to technologies developed by others. These increasing incentives to differentiate the task of invention from that of commercializing new technologies depended for their realization upon the development of markets and other types of organizational supports for trade in technology. The evidence suggests that the necessary institutions evolved first in those regions of the country where early patenting activity had already been concentrated. A self-reinforcing process whereby high rates of inventive activity encouraged the evolution of a market for technology, which in turn encouraged greater specialization and productivity at invention as individuals found it increasingly feasible to sell and license their discoveries, appears to have been operating. This market trade in technological information was an important contributor to the achievement of a high level of specialization at invention well before the rise of large-scale research laboratories in the twentieth century.

Role for cells in the presupplementary motor area in updating motor plans.

Two motor areas are known to exist in the medial frontal lobe of the cerebral cortex of primates, the supplementary motor area (SMA) and the presupplementary motor area (pre-SMA). We report here on an aspect of cellular activity that characterizes the pre-SMA. Monkeys were trained to perform three different movements sequentially in a temporal order. The correct order was planned on the basis of visual information before its execution. A group of pre-SMA cells (n = 64, 25%) were active during a process when monkeys were required to discard a current motor plan and develop a plan appropriate for the next orderly movements. Such activity was not common in the SMA and not found in the primary motor cortex. Our data suggest a role of pre-SMA cells in updating motor plans for subsequent temporally ordered movements.